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Biomedical subjects

J Bender

Publications and source records attributed to J Bender.

At least 55 records · Page 3Linked to original sources
PubMed1999

Surgical intervention and understanding of diseases of the stomach and duodenum.

The stomach and duodenum are organs of complex physiology and cell biology. Neoplastic disease of these organs represents a difficult surgical challenge, and gastric and duodenal cancer mortality rates remain high despite advances in surgical technique, perioperative care, and adjuvant therapy. True "cures" elude the surgeon all too often. Fortunately, our understanding of the genetics and molecular biology of upper gastrointestinal neoplasms is increasing and is now significantly affecting the clinical management of these tumors as surgical therapies continue to improve. The care of benign disease of the stomach and duodenum is also evolving as medical therapy and surgical technology improve to lessen the morbidity associated with peptic ulcer disease and other benign conditions. The event that may have the greatest effect on surgical intervention in peptic ulcer disease is the Centers for Disease Control and Prevention launching of an educational campaign to promote treatment of Helicobacter pylori. This article reviews the most significant advances published in the past year on surgical intervention of the stomach and duodenum.

Journal Article↗
PubMed1998

The DNA methylation locus DDM1 is required for maintenance of gene silencing in Arabidopsis.

To investigate the relationship between cytosine methylation and gene silencing in Arabidopsis, we constructed strains containing the ddm1 hypomethylation mutation and a methylated and silenced PAI2 tryptophan biosynthetic gene (MePAI2) that results in a blue fluorescent plant phenotype. The ddm1 mutation had both an immediate and a progressive effect on PAI gene silencing. In the first generation, homozygous ddm1 MePAI2 plants displayed a weakly fluorescent phenotype, in contrast to the strongly fluorescent phenotype of the DDM1 MePAI2 parent. After two generations of inbreeding by self-pollination, the ddm1/ddm1 lines became nonfluorescent. The progressive loss of fluorescence correlated with a progressive loss of methylation from the PAI2 gene. These results indicate that methylation is necessary for maintenance of PAI gene silencing and that intermediate levels of DNA methylation are associated with intermediate gene silencing. The results also support our earlier hypothesis that ddm1 homozygotes act as "epigenetic mutators" by accumulating heritable changes in DNA methylation that can lead to changes in gene expression.

Arabidopsis↗
PubMed1998

A Myb homologue, ATR1, activates tryptophan gene expression in Arabidopsis.

In Arabidopsis thaliana, tryptophan pathway genes are induced in response to starvation, wounding, and pathogen attack, resulting in increased production of tryptophan and secondary metabolites important for development and defense. The Arabidopsis tryptophan pathway therefore provides an ideal system for elucidating how environmental stimuli are transduced into changes in plant gene expression. To characterize the factors that regulate the first gene in the pathway, ASA1, which is the key point of control, we have isolated altered tryptophan regulation (atr) mutants with deregulated expression of ASA1. One of these mutants, atr1D is dominant for increased transcription of ASA1 in specific seedling tissues. We have used atr1D to clone the ATR1 gene based on its map position. ATR1 encodes a Myb-like transcription factor that modulates ASA1 expression. The ATR1 transcript also includes a 5' regulatory region with three short ORFs, one of which is prematurely terminated by the atr1D mutation. Thus, ATR1 defines the first characterized tryptophan gene regulator in plants, and the atr1D mutation defines a sequence important for ATR1 expression.

Amino Acid Sequence↗
PubMed1998

An assessment of approximating aspheres with more easily manufactured surfaces.

In designing optical systems for synchrotron radiation, one is often led to conclude that optimal performance can be obtained from optical surfaces described by conic sections of revolution, usually paraboloids and ellipsoids. The resulting design can lead to prescriptions for three-dimensional optical surfaces that are difficult to fabricate accurately. Under some circumstances satisfactory system performance can be achieved through the use of more easily manufactured surfaces such as cylinders, cones, bent cones, toroids and elliptical cylinders. These surfaces often have the additional benefits of scalability to large aperture, lower surface roughness and improved surface figure accuracy. In this paper we explore some of the conditions under which these more easily manufactured surfaces can be utilized without sacrificing performance.

Journal Article↗
PubMed1998

Manufacturing advances in large grazing-incidence optics.

The fabrication of large grazing-incidence mirrors imposes needs for special fabrication and coating equipment, facilities, and raw materials. The economic realization of such optics has been readily accomplished through close interactions between the mirror users, the fabricator and the manufacturer of the raw material designated as mirror substrate. The manufacture and delivery of a 1.4 m flat and 1.0 m conical mirror are used to provide examples of recently demonstrated manufacturing technologies and effective interactions between participating organizations.

Journal Article↗
PubMed1998

Cytosine methylation of repeated sequences in eukaryotes: the role of DNA pairing.

In eukaryotic genomes, methylation of cytosine residues commonly occurs in repetitive sequences. This methylation correlates with reduced gene expression and suppression of recombination, and is thus thought to serve as a genome-defense mechanism that guards against the deleterious effects of multicopy transposable elements and aberrant gene duplications. Analysis of methylation in fungi and plants suggests that the ability of DNA repeats to pair with one another is a key to their selection for methylation. Recent data have outlined the substrate requirements for the establishment and maintenance of methylation in eukaryotic repeated sequences. Substrate-methylation patterns could help us to understand the way in which methyltransferase enzymes recognize their substrates.

Arabidopsis↗
PubMed1998

T-cell survival.

Like other cells, T cells are dependent on signals from their environment for their survival. Resting T cells are supported in vitro by cytokines such as interleukin (IL)-4, IL-6 and IL-7. The latter two cytokines are made constitutively in animals and hence might affect the lifetimes of their resting T cells. Resting T cells are also kept alive by interaction with an as yet unidentified molecule on the surface of other cells. Activated T cells are also supported in vitro by members of two families of these proteins, the IL-2 family and the interferon-alpha beta family. Members of the latter family may have effects on activated cells in vivo. Thus although both resting and activated T cells require signals to keep themselves alive, the signals are different for the two types of cells. This perhaps allows the immune response to control the numbers of activated cells during infections without compromising its pool of precursor, resting T cells.

Animals↗
PubMed1997

The telomere binding protein of Euplotes crassus prevents non-specific transcription initiation but has no role in positioning transcription initiation complexes.

Model substrates mimicking the telomeric as well as the 5'-untranslated regions in front of a 5'-terminal part of a macronuclear gene of Euplotes crassus were transcribed in vitro using cellular extracts. The obtained transcripts were characterized by primer extension and shown to start at the natural initiation points. The situation changed in the absence of telomere binding protein or with substrates lacking functional telomeric sequences. In these cases non-specific transcription was observed. Since it had been previously found that transcription starts are frequently located at an apparently fixed distance from the telomere, a model substrate was constructed which carried a duplication of the non-transcribed region. This resulted in only one transcription start site, the position of which was conserved relative to the start of the open reading frame but moved away from the telomere by the distance of the duplication.

Animals↗
PubMed1997

Cerivastatin: pharmacology of a novel synthetic and highly active HMG-CoA reductase inhibitor.

The pyridine derivative cerivastatin is a new entirely synthetic and enantiomerically pure inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. As a sodium salt cerivastatin is present in the active, open ring form. Cerivastatin inhibited the membrane-bound (non-solubilized) HMG-CoA reductase of the native microsomal fraction isolated from rat liver with a Ki value of 1.3 x 10(-9) M. The reference compound lovastatin was 100-fold less potent and exhibited a Ki value of 150 x 10(-9) M. Cerivastatin inhibited the cholesterol synthesis in the human hepatoma cell line HepG2 cells with a similar IC50 value of 1.0 x 10(-9) M. In vivo studies reflected its high in vitro activity. In both rats and dogs, cerivastatin inhibited the hepatic [14C]cholesterol synthesis from [14C]acetate with an oral ED50 value of 0.002 mg/kg body weight, while lovastatin exhibited an oral ED50 value of 0.3 mg/kg in rats, showing again the ratio of 100 or more between cerivastatin and lovastatin. In the small intestine and testes, cerivastatin was at least 50-fold less active with oral ED50 values higher than 0.1 mg/kg, which is indicative for a high liver selectivity of cerivastatin. In cholestyramine-primed dogs cerivastatin dose-dependently lowered the serum cholesterol concentrations by up to 59% with 0.1 mg/kg after 20 days. Interestingly, the serum triglycerides were markedly reduced by 53 and 76% with 0.03 and 0.1 mg/kg, respectively. In normal chow fed dogs the low density lipoprotein (LDL) concentrations were reduced by up to 75% after 0.1 mg cerivastatin/kg. The ratio of HDL/LDL increased by 81% compared with a change of only 14% in the placebo treated control group. The antiatherogenic effect of cerivastatin was shown in rabbits fed a diet enriched with 0.2% cholesterol. After 9 weeks on diet 0.1 mg cerivastatin/kg decreased the accumulation of cholesterol ester in the arterial tissue by 73%. In summary, these data as compared to published data on other HMG-CoA reductase inhibitors demonstrate cerivastatin to be the most active compound in this class. Vastatins used in therapy are effective in mg doses, while cerivastatin offers a new low dose therapy in the microg range.

Administration, Oral↗
PubMed1996

Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.

PURPOSE: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.

Adolescent↗
PubMed1995

Epigenetic control of an endogenous gene family is revealed by a novel blue fluorescent mutant of Arabidopsis.

The Wassilewskija strain of Arabidopsis has four genes encoding the tryptophan enzyme phosphoribosylanthranilate isomerase (PAI) located at three unlinked sites. These four PAI genes are methylated over their regions of DNA homology. When PAI copy number is reduced by deletion of two tandemly arrayed genes (MePAI1-PAI4), a mutant with fluorescent, tryptophan-deficient phenotypes results, because the two remaining methylated PAI genes (MePAI2 and MePAI3) supply insufficient PAI activity. These two methylated genes can be inherited through meiosis, even when they are segregated away from each other in crosses to a strain with unmethylated PAI genes. However, the mutant phenotypes conferred by the methylated PAI genes are unstable, and mutant plants yield occasional revertant somatic sectors and progeny. Revertant lines display coordinately reduced methylation of both PAI2 and PAI3, implying that this hypomethylation acts in a concerted manner across the genome rather than at individual sites.

Aldose-Ketose Isomerases↗
PubMed1995

Human dermal endothelial cells express membrane-associated mast cell growth factor.

Mast cell growth factor (MGF), a molecule that serves as a ligand for the receptor tyrosine kinase c-kit, is important in mast cell differentiation, migration, and activation. Previous studies of paraffin-embedded human skin using antibody to murine MGF and reverse transcription-polymerase chain reaction have demonstrated MGF protein and mRNA expression in keratinocytes and isolated dermal cells. We utilized a monoclonal antibody to human MGF to further define patterns of immunoreactivity in frozen specimens of neonatal and adult skin from normal individuals and from patients with urticaria pigmentosa. In addition to keratinocytes and isolated dermal cells in normal and urticaria pigmentosa skin, MGF was detected in cells lining superficial and mid-dermal vessels. Co-expression of MGF and the vascular antigen CD31, and immunoelectron microscopy, identified MGF-positive cells as endothelial cells. Patterns of endothelial MGF expression were not influenced by mast cell degranulation and endothelial E-selectin induction in vitro. By ultrastructure, unfixed specimens demonstrated MGF expression both within the endothelial cytoplasm and in association with lumenal, but not ablumenal, surfaces. Specimens fixed with Nakane's solution had diminished endothelial cytoplasmic MGF reactivity, but lumenal expression was maintained, suggesting persistence of a membrane-associated reactivity. MGF mRNA was also detected in cultured dermal microvascular endothelial cells using reverse transcription-polymerase chain reaction. These data establish human dermal endothelial cells as sites of MGF production and expression in human skin. Mast cell precursors must home to skin via vascular channels and differentiate in the immediate perivascular space. Thus, endothelial MGF may be an important determinant of adhesion and differentiation of mast cell progenitors expressing receptors for MGF.

Adult↗
PubMed1995

A phase I trial of interleukin 3 (IL-3) pre-bone marrow harvest with granulocyte-macrophage colony-stimulating factor (GM-CSF) post-stem cell infusion in patients with solid tumors receiving high-dose combination chemotherapy.

In humans, interleukin 3 (IL-3) administration increases the cellularity and cycling of bone marrow progenitor cell populations. Initially, in primates and then in humans, IL-3 in sequence with GM-CSF has been shown to stimulate multilineage hematopoiesis. Based upon these effects, we designed a phase I trial of daily IL-3 administered subcutaneously for 10 days at dose levels of 2.5, 5.0, 10.0, 12.5, and 15.0 micrograms/kg followed within 72 h by bone marrow harvest, high-dose chemotherapy, and following chemotherapy, a fixed dose (5.0 micrograms/kg/day) of GM-CSF and bone marrow rescue. The study was designed to assess the toxicity and biological effects of IL-3 administered alone prior to bone marrow harvest and to determine the safety and clinical effects of IL-3 stimulated bone marrow with GM-CSF following high-dose combination chemotherapy. A total of 19 patients with chemotherapy-sensitive non-hematologic malignancies (13 breast, five ovarian, and one testicular cancer) were enrolled. IL-3 up to 15.0 micrograms/kg/day could be administered without dose-limiting toxicities. Flu-like symptoms and headaches were common and poorly tolerated at the highest IL-3 dose. Significant increases in neutrophil counts (P = 0.018) were observed following IL-3. Overall, IL-3 administration was associated with a modest, but significant increase in CFU-GM within the bone marrow (P = 0.034). IL-3 administration had no consistent effect on CD34+ cell number within bone marrow. For the entire group, engraftment of neutrophils to greater than 0.5 x 10(9)/l occurred at a median of 21 days (range of 13-63 days) and platelet independence occurred at a median of 17 days (range 11-120 days). When IL-3 dose levels were analyzed separately, engraftment of neutrophils and platelets, blood product (platelets and packed RBCs) utilization, and discharge date were not superior in those treated with the higher dose (15.0 micrograms/kg) of IL-3. While higher doses of IL-3 were associated with more toxicity, they did not appear to enhance the stem cell pool or speed engraftment later. The effects of pre-bone marrow harvest IL-3 are modest and likely not as impressive as other approaches aimed at enhancing hematologic recovery following high-dose chemotherapy.

Adolescent↗
PubMed1994

AFC1, a LAMMER kinase from Arabidopsis thaliana, activates STE12-dependent processes in yeast.

In the yeast Saccharomyces cerevisiae a kinase cascade activates the transcription factor STE12 leading to mating in haploid cells and pseudohyphal growth in diploid cells. To investigate related signal transduction pathways in higher plants, we have isolated a putative protein kinase gene from Arabidopsis thaliana that restores STE12-dependent functions to yeast with mutations in this signal transduction pathway. This Arabidopsis gene, AFC1, induces three STE12-dependent processes even in signal transduction-defective yeast strains: mating-specific gene expression in haploid yeast, mating of haploid yeast to yield diploids, and pseudohyphal growth in diploid yeast. AFC1 has no effect on transcription of the STE12 gene and, instead, is likely to activate the STE12 protein. However, AFC1 has only limited homology to FUS3 and KSS1, the endogenous yeast kinase regulators of STE12. AFC1 is a member of a recently described CDC2-related kinase subfamily, the LAMMER kinases. A close AFC1 homolog, AFC2, lacks STE12 activation phenotypes, indicating the specificity of AFC1. The phenotypes of AFC1 in yeast provide us with tools to elucidate the role of this kinase in Arabidopsis.

Amino Acid Sequence↗
PubMed1994

Response of cellular antioxidants to ozone in wheat flag leaves at different stages of plant development.

The effect of ozone (O3) on growth, yield and foliar antioxidants of spring wheat (Triticum aestivum L. cv. Turbo) was investigated in 1990 and 1991 in Braunschweig, Germany. Plants were grown full-season in pots in open-top chambers ventilated with charcoal-filtered (CF) air to which one or two levels of O3 were added. Mean 8 h day(-1) (10.00-18.00 h) O3 concentrations in the CF and CF + O3 treatments were 5.9, 61.2 and 92.5 nl litre(-1) in 1990, and 4.7 and 86.4 nl litre(-1) in 1991. Plants that received the high O3 level showed symptoms of premature senescence of the oldest leaves and yield reductions in both growing seasons. The contents of ascorbate and glutathione and the enzyme activities of ascorbate peroxidase and glutathione reductase were measured in symptomless flag leaves in weekly intervals before and after the beginning of anthesis. Leaf age had a significant effect on all antioxidants investigated. The O3 exposures of about 90 nl litre(-1) increased the activity of ascorbate peroxidase and the concentration of glutathione, but there were no pollutant effects on ascorbate content and glutathione reductase activity. Measurements of the antioxidant levels throughout one day showed no clear indications of diurnal changes in the antioxidative capacity in wheat flag leaves. The results are discussed in relation to the role of antioxidants in O3 detoxification.

Journal Article↗